The aim of this study is to determine whether a metabolic defect in the adenylate cyclase/cAMP/protein kinase A signal transduction pathway exists in the T lymphocytes of subjects with the autoimmune disorder, Systemic Lupus Erythematosus. Our results demonstrated a disorder of protein kinase A function, resulting in deficient protein kinase A-dependent phosphorylation of intracellular proteins. This was the first identification of a metabolic pathway defect in lymphocytes.